Characterization of a third generation lentiviral vector pseudotyped with Nipah virus envelope proteins for endothelial cell transduction.
Characterization of a third generation lentiviral vector pseudotyped with Nipah virus envelope proteins for endothelial cell transduction.
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慢病毒作为基因治疗载体越来越受欢迎，因为它们能够整合到静止细胞中，而且最近的临床试验取得了成功。将这些载体导向特定的细胞类型并限制体内脱靶转导仍然是一个挑战。替换负责细胞结合或假分型的病毒包膜蛋白仍然是改善慢病毒靶向性的常用方法。在这里，我们描述了高滴度，第三代慢病毒载体假型尼帕病毒融合蛋白（NiV-F）和附着蛋白（NiV-G）的发展。对高滴度至关重要的是NiV-F和NiV-G细胞质结构域的截断。作为已知的野生型尼帕病毒靶点，原代内皮细胞被尼帕假病毒有效地转导。相比之下，人CD34+造血祖细胞没有明显的转导。此外，与VSV假型慢病毒相比，尼帕假型病毒在人血清中的稳定性更高。这些发现表明，在第三代慢病毒载体中使用尼帕病毒包膜蛋白将是一种有价值的靶向内皮细胞基因递送工具。
Lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. Directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. Replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. Here, we describe the development of a high titer, 3rd generation lentiviral vector pseudotyped with Nipah virus fusion protein (NiV-F) and attachment protein (NiV-G). Critical to high titers was truncation of the cytoplasmic domains of both NiV-F and NiV-G. As known targets of wild-type Nipah virus, primary endothelial cells are shown to be effectively transduced by the Nipah pseudotype. In contrast, human CD34+ hematopoietic progenitors were not significantly transduced. Additionally, the Nipah pseudotype has increased stability in human serum compared to VSV pseudotyped lentivirus. These findings suggest that the use of Nipah virus envelope proteins in 3rd generation lentiviral vectors would be a valuable tool for gene delivery targeted to endothelial cells.
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